Endoscope apparatus, actuators, and methods therefor

ABSTRACT

The present invention provides, in part, a dexterous endoscope apparatus, referred to herein as a MicroFlex Scope (MFS). The MFS is an novel, small diameter, e.g., less about 1 mm to about 4 mm, about 1 mm to about 3 mm, etc., dexterous endoscope that allows for access, direct visualization, tissue sampling, treatment, etc. of body lumens. In one embodiment, the distal end of the MFS of the invention is an ultra-flexible tip that comprises a plurality of thin, curved shape memory alloy (SMA) actuator elements attached to at least one structural skeleton, e.g., a coil spring skeleton or hinge structure. The SMA actuator elements in each structural skeleton segment are indirectly heated by a heater element and produce force in response to their temperature relative to specific thresholds. In certain embodiments, the heater element may include an integrated heater/sensor element adapted to heat the actuator element and to sense the temperature and bend state of the actuator element. In configurations comprising a plurality of actuator elements, multiplexing/demultiplexing of heating currents and sensor voltages may be accomplished via a parallel bus and demulitplexing circuit. In this regard, a demultiplexing circuit using standard microelectronic fabrication techniques may be designed to achieve individual sensing and control over each actuator element.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH OR DEVELOPMENT

The government has rights in this invention arising from NationalInstitutes of Health STTR Grant Nos. 1 R41 HL083331-01 and 1 R41AI063892-01, that partially funded the research leading to thisinvention.

BACKGROUND OF THE INVENTION

In recent years there has been increasing use of endoscopes forminimally invasive treatment and diagnosis. For example, endoscopes areoften used in diagnostic procedures in an attempt to visualize anddiagnose problems in the sinus structures, as well as in sinussurgeries. Due to its proximity to sensitive orbital and cerebralstructures, access, visualization, and surgeon confidence all factorinto clinical efficacy, patient safety and minimizing complications indiagnosing and performing surgery in this challenging anatomical area.However, current endoscopes, and related instrumentation do not providethe flexibility, dexterity and small enough diameter to access, directlyvisualize, and effectively perform sensitive procedures throughout allsinus structures.

Chronic sinusitis affects approximately 33 million Americans each year,and has become one of the most prevalent chronic diseases. SeeBajracharva H, Hinthorn D. “Sinusitis, Chronic”www.emedicine.com/med/topic2556.htm. Chronic sinusitis is generallycharacterized as sinusitis lasting longer than 3 months despitetreatment, and/or four recurrences of acute sinusitis. The prevalence ofchronic sinusitis is likely to grow with increasing pollution, urbansprawl and resistance to antibiotics. See id.

Because of its persistent nature, chronic sinusitis has become asignificant cause of morbidity and involves considerable expense to theworldwide health care system. Chronic sinusitis results in 18 to 22million U.S. physician office visits annually (See “Adult ChronicRhinosinusitis: Definitions, Diagnosis, Epidemiology, andPathophysiology,” Otolaryngology—Head & Neck Surgery, Supplement, (2003)September: 129: S1-84), and, in 2001, resulted in 1.3 million documentedvisits to hospital outpatient facilities. See National HospitalAmbulatory Medical Care Survey: 2001 Outpatient Department Summary. Itwas the most frequently reported chronic disease in the 1993 NationalHealth Interview Survey, affecting 14.7% of the population and was thefifth most common use of antibiotics. See Sinusitis, American Academy ofAllergy, Asthma and Immunology,www.aaaai.org/patients/resources/fastfacts/sinusitis.stm. In 2002,Sinusitis accounted for 9% of all pediatric and 21% of all adultantibiotic prescriptions and, thus, contributes to the increasing rateof antibiotic resistance. See “Antimicrobial Treatment Guidelines forAcute Bacterial Rhinosinusitis,” Otolaryngology—Head & Neck SurgerySupplement (2004) January; 130: 1-49. Untreated sinusitis affectspersonal productivity and quality of life. It is associated withexacerbation of asthma and serious complications, such as brain abscessand meningitis, which can produce significant morbidity and mortality.See Bajracharva H, Hinthorn D. “Sinusitis, Chronic”www.emedicine.com/med/topic2556.htm. While some individuals can besuccessfully treated with medications, others require surgery.

Millions of diagnostic procedures are conducted each year to attempt tovisualize and diagnose problems in the sinus structures. In 2001,approximately 200,000 sinus surgeries were performed in the U.S. See id.The surgeries were performed to treat chronic sinusitis, as well as forexcision of tumors and polyps, cerebrospinal fluid (CSF) leak closure,orbital and optic nerve decompression, dacryocystorhinostomy, choanalatresia repair, foreign body removal and epistaxis repair. See Patel A,Vartanian J, Guzman Portugal L. “Functional Endoscopic Sinus Surgery”www.emedicine.com/ent/topic758.htm. The difficulty visualizing andaccessing certain areas of the sinus structures, particularly thefrontal and the ethmoid sinuses, the proximity of the sinus to sensitivestructures, such as the orbit and neurovascular structures, and thepresence of abnormal growths or anatomy can cause sinus surgery to bechallenging, time consuming, and subject to serious complications.Complications can include: orbital injury or hematoma; bleeding;infection; synechiae formation; CSF leaks; direct brain injury; denudedbone resulting in delayed healing; and diplopia. See Patel A, VartanianJ, Guzman Portugal L. “Functional Endoscopic Sinus Surgery”www.emedicine.com/ent/topic758.htm; Rombout J, deVries N. “Complicationin Sinus Surgery and new Classification Proposal.” American Journal ofRhinology (2001) 25:280-286; Kennedy D. “Functional Endoscopic SinusSurgery: Concepts, Surgical Indications, and Instrumentation,” Diseasesof the Sinuses, Elsevier, 2000, pp. 197-210.

While the incidence of major complications during sinus surgery is low(see Rombout J, deVries N. “Complication in Sinus Surgery and newClassification Proposal.” American Journal of Rhinology (2001)25:280-286), complications such as orbital damage and CSF leaks cancause significant morbidity when they do occur. See Rene C, Rose G,Letnall R, Moseley I. “Major orbital complications of endoscopic sinussurgery” British Journal of Ophthalmology (2001) May 85:598-603. Insurgically challenging frontal sinusotomy procedures, damagingexploration or inadvertent stripping of mucosa can result in prolongedmorbidity and multiple surgical procedures. See Kennedy D. “FunctionalEndoscopic Sinus Surgery: Concepts, Surgical Indications, andInstrumentation,” Diseases of the Sinuses, Elsevier, 2000, pp. 197-210.

The second largest cause of failure in endoscopic maxillary sinussurgery identified in Richtsmeier's study was ethmoid/frontal diseasethat couldn't be visualized on a CT scan. See Richtsmeier W J. “Top 10Reasons for Endoscopic Maxillary Sinus Surgery Failure,” Laryngoscope(2001) November 111:1952-6. Other studies have highlighted the role ofincomplete ethmoid dissection and post-operative scarring in the frontaland ethmoid sinuses as important factors in surgical failure. SeeRamadan H. “Surgical Causes of Failure in Endoscopic Sinus Surgery,”Laryngoscope 1999; 109:27-9; Shah, N. “Functional Endoscopic SinusSurgery,” www.bhj.org/journal/1999_(—)4104-Oct99/SP_(—)659.HTM. Directaccess, clear visualization, and surgeon confidence can all affectoutcomes. As such, improved endoscopes are needed that would be smaller,more dextrous, more flexible and allow the physician greater access,visualization and the ability to perform procedures in all of the sinusstructures.

Bronchoscopy using endoscopes is also a proven method of directlyvisualizing the airways of the lung and sampling suspicious tissue.However, current diameters of endoscopes (e.g., ranging from 2.2 mmultra thin visualization only scopes up to 6.2 mm) prevents access anduse in over half the area of the lung. While other forms of testing haveevolved (laser induced fluorescence endoscope (LIFE) airway imaging,endobronchial ultrasound, virtual bronchoscopy, spiral CT, CT withnodule enhancement and PET scan), none of the methods offer the uniqueand significant advantages of conventional bronchoscopy, i.e., directvisualization for accurate location, and collection of tissue sampleswith minimal safety concerns.

In the United States, the new, diagnosed cases of cancer of the lung andbronchus were estimated at approximately 174,000 in 2003. See Jemal A,Tiwari R, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin(2004) 54: 8-29. U.S. populations of current and ex-smokers (50 millioneach) make it probable that this significant health problem willcontinue. See American Cancer Society. (1999) Cancer Facts and Figures,1999. American Cancer Society Atlanta, Ga.

Lung cancer is the most common cause of cancer deaths in the U.S.,accounting for more deaths in 2000 than from prostate, breast, andcolorectal cancer combined. Less than 15% of patients survive 5 yearsafter diagnosis. The poor prognosis is largely attributable to the lackof effective early detection methods and the inability to curemetastatic disease. Early diagnosis and treatment of lung cancer cansignificantly improve the patient's chances of survival. See Naruke, T,Tsuchiya, R, Kondo, H, et al (1997) Implications of staging in lungcancer. Chest 112(suppl) 4, 242S-248S; Mountain, C F, Dresler, C M(1997) Regional lymph node classification for lung cancer staging. Chest111, 1718-1723. Patients with the most favorable clinical stage, IAdisease, have a 5-year survival of about 60%, while those with moreadvanced disease, clinical stage II-IV, have 5-year survival ratesranging from 40% to less than 5%.

Clearly, early identification and intervention are key to improving curerates. Currently, however, over two-thirds of the patients diagnosedhave regional lymph-node involvement or distant disease at diagnosis.See Ihde D. C. Chemotherapy of lung cancer, N. Engl. J. Med., 327:1434-1441, 1992. The solution requires a shift in the therapeuticparadigm from targeting advanced clinically manifest lung cancer toidentifying asymptomatic, preinvasive and early-invasive lesions,coupled with accurate diagnosis and staging.

Bronchoscopy is one of the most commonly used diagnostic and therapeuticprocedures in pulmonology, and is routinely used to screen a subgroup ofpatients at high risk for lung cancer, including those with a) riskfactors (emphysema, family history, environmental exposures), b)atypical sputum cytology, or c) suspicious chest x-ray. These proceduresare well-tolerated by most patients using local anesthesia and conscioussedation, with exam times of 20-45 minutes, which refined techniques canextend to 60-120 minutes without compromising patient comfort. Directvisualization of the airways can localize potential abnormalities of thetracheobronchial mucosa. The characteristics of these abnormalities(color, stiffness, vascularization, smooth margins, etc.) help toestablish the diagnosis and direct treatment. The channels of theflexible bronchoscope support the removal of secretions and samplesthrough bronchial washing, brushing, and biopsy to establish histologicdiagnosis, with an average diagnostic yield of 90% for central lungcancers. See Mazzone, P., Jain, P., Arroliga, A. C., Matthay, R. A.,Bronchoscopy and Needle Biopsy Techniques for Diagnosis and Staging ofLung Cancer. Clinics in Chest Medicine. 23:137-158, 2002; C. Agusti, A.Xaubet, “Bronchoscopic procedures in the new millennium”www.personal.u-net.com/˜ersj/Buyers %20Guide %20for %20the%20Internet/agusti37-38.html.htm.

The current size (diameter) of conventional bronchoscopes have limitedthe ability to access the majority of the lung. Reductions in the sizeof the developmental bronchoscope have demonstrated success in expandingits reach and capabilities. See Schoenfeld, N., et. al., UltrathinBronchoscopy as a New Tool in the Diagnosis of Peripheral Lung Lesions,Lung Cancer Frontiers, No. 9, October 2000; Rooney, C. P., Wolf, K.,McLennan, G. Ultrathin Bronchoscopy as an Adjunct to StandardBronchoscopy in the Diagnosis of Peripheral Lung Lesions, Respiration,69:1, 2002.

Although desirable, it is currently impractical to use bronchoscopy toscreen the general population or to examine small bronchioles. However,since bronchoscopy is currently part of a routine protocol for high riskpopulations, it would be desirable to expand access into the bronchialtree to more areas where lung cancer predominates, such as the upperlobes, or to targeted areas identified by CT. See Byers T E, Vena J E,Rzepka T F. “Predilection of Lung Cancer for the Upper Lobes: AnEpidemiologic Inquiry,” J Natl Cancer Inst. 1984 June; 72(6): 1271-5.Thus, additional improvements in bronchoscopes are needed.

Some recent efforts have focused on developing endoscopes with activecatheters in which a shape memory alloy (SMA) that is deformable whenelectrically heated is utilized as actuator elements. For example, JPLaid-Open publication No. H11-48171 published Feb. 23, 1999 proposes anactive catheter of an outer skeleton type in which a liner coil isdisposed outside of a plurality of coiled actuators which are made of ashape memory alloy. The SMA actuators are directly electricallyenergized to permit the active catheter to be bent or flexed. U.S. Pat.No. 6,672,338 also discloses an active catheter having a linear coilforming an elastically deformable skeletal structure and a coil springactuator made of shape memory alloy. However, improvements in endoscopedesign and actuation are still needed.

BRIEF SUMMARY OF THE INVENTION

The present invention is generally directed to actuator elements,actuated structural skeletons, endoscope apparatus including suchactuator elements, and methods of using and making the same.

In a first aspect, an actuator element is provided. In certainembodiments, the actuator elements of the inventions generally comprise:a flat shape memory alloy (SMA) layer adapted to exhibit a variation inbend state corresponding to a variation in temperature of the SMA layer;an integrated heater/sensor layer interfaced with said SMA layer; and ademultiplexing circuit and parallel bus interfaced with saidheater/sensor layer. The heat/sensor layer is adapted to indirectly heatthe SMA layer upon application of current to the heater/sensor layer, tosense the temperature and bend state of the SMA layer, and to produce avoltage in proportion to the sensed temperature and bend state of theSMA layer. Further, the demultiplexing circuit and parallel bus areadapted to allow for connection of multiple actuator elements therebyenabling communication and control of individual actuator elements whenmultiplexed with a plurality of actuator elements. In some embodiments,the parallel bus comprises a multi-wire flex cable bus system configuredto interconnect multiple actuator elements.

In another aspect, a method of making an actuator element of theinvention is provided. The method generally comprises: providing a SMAlayer temporarily fixed to a first carrier substrate; and providing anintegrated heater/sensor/demultiplexer layer fixed to a second siliconsubstrate. The two substrates are bonded face-to-face using a siliconegel adhesive, and the second silicon substrate is removed from theheater/sensor layer via silicon back-side etch process. The adhesivesecuring the cured SMA/heater/sensor/demuliplexer alignment to the firstsilicon substrate is removed to thereby result in a completedSMA/heater/sensor/demultiplexer actuator element.

In certain embodiments, the demultiplexing circuit and parallel buscomprises a multi-wire flex cable bus, demultiplexing circuit chips, andheater/sensor elements. In such embodiments, the method for making thedemultiplexing circuit chips, parallel bus, and heater/senor layers mayoptionally comprise: constructing the demultiplexing circuits on asilicon substrate using metal oxide semiconductor processes, such asphotolithographic patterning, oxidation, dopant diffusion orimplantation, and metal sputtering or evaporation; depositing andpatterning alternate layers of polyimide and metal over saiddemultiplexing circuits to thereby provide said multi-wire bus andheater/sensor layers; and selectively removing the silicon substrate viaback-side etching to thereby provide separate demultiplexing circuitsand heater/sensor layers, connected by the parallel bus.

In yet another aspect of the invention, an actuated coil segment isprovided. The actuated coil segments of the invention may comprise: aplurality of shape memory alloy (SMA) actuator elements interconnectedvia a lattice structure adapted to provide skeleton attachment points;and a coil spring skeleton secured to the plurality of SMA actuatorelements via the attachment points of the lattice structure. In certainembodiments, the SMA actuator elements comprise a SMA layer interfacedwith an integrated heater/sensor layer configured so as to indirectlyheat the SMA layer. The SMA actuator elements may be interconnected in alattice structure, and the lattice structure is secured to the SMA coilskeleton such that the coil skeleton contacts the lattice structure atattachment pints, and abuts the lattice structure at other load-bearingpoints.

In yet another aspect, a method of making an actuated coil segment ofthe invention is provided. Such methods generally comprise: providing aplurality of SMA actuator elements as an interconnected latticestructure to provide skeleton attachment points and providing the SMAcoil skeleton located about its exterior perimeter to a copper weldingprobe and interior copper mandrels adapted to act as resistance weldingelectrodes; wherein the ends of the SMA coil skeleton are secured totension fixtures at their distal ends to thereby provide axial tensionto the SMA coil skeleton and compression forces between copperelectrodes while located on the welding fixture. The SMA coil skeletonlocated on the welding mandrel is then aligned relative to the SMAactuator lattice structure such that the coil skeleton attachment andload-bearing features interface with the corresponding features on theSMA lattice. The copper mandrel is rolled relative to the SMA actuatorlattice structure while selectively energizing the copper mandrel andwelding proble at locations corresponding to the skeleton attachmentspoints so as to form spot welds at said attachment points. The proximalends of the SMA coil skeleton are then released from tension fixturesfollowing formation of said spot welds, thereby allowing the axialtension in the SMA coil skeleton to compress the plurality of SMAactuator elements inward, resulting in a compressed state coil segment.

In yet another aspect of the invention, a microdexterous endoscopeapparatus is provided. The endoscope apparatus generally comprises: acatheter having a lumen comprising at least one port in the interior ofsaid lumen; at least one actuated coil segment at the distal end of thecatheter comprising at least one port in the interior of said actuatedcoil segment; a control system configured to monitor and controlactuation of at least one coil segment based at least in part ontemperature and strain feedback from said actuated coil segment; and anelectrical bus traversing the length of the catheter and interfacingwith said at least one actuated coil segment and said control system. Incertain embodiments, the actuated coil segment comprises a plurality ofindirectly heated shape memory alloy (SMA) actuators secured to a SMAcoil skeleton, wherein each SMA actuator is adapted to exhibit avariation in bend state corresponding to a variation in temperature ofthe SMA actuator. Further, the control system is preferably adapted tomodulate application of a current to thereby independently control thetemperature of the plurality of SMA actuators to achieve a desired bendstate based at least in part on a non-linear hysteresis control modelusing feedback voltages obtained from the SMA actuator via theelectrical bus.

In yet other aspects of the invention, methods for the directvisualization of a body lumen are provided. Such methods generallycomprise: inserting the catheter of an endoscope of the invention into asubject comprising a body lumen to be visualized; manipulating placementof the distal end of said catheter in the body lumen to be visualizedvia said at least one actuated coil segment; and directly visualizingsaid body lumen via the image guide. In certain embodiments, the bodylumen is selected from the group consisting of lung airways, bronchialairways, and sinus cavities.

In other aspects, the catheter comprises at least two ports, and thesecond port comprises a tool configured to sample tissue. In suchembodiments, the methods of the inventions may further comprise:manipulating placement of the distal end of said catheter via said atleast one actuated coil segment to thereby locate said tissue samplingtool at a desired location; and obtaining a tissue sample via saidtissue sampling tool.

In other aspects, the catheter comprises at least three ports, one portfor the image guide, one for the tool, and one for vacuum/flush/drugdelivery. Again, in such embodiments, the methods of the inventions mayfurther comprise: manipulating placement of the distal end of saidcatheter via said at least one actuated coil segment to thereby locatesaid tissue sampling tool at a desired location; and obtaining a tissuesample via said tissue sampling tool.

These and other aspects of the invention will become apparent to thoseskilled in the art with reference to the detailed description anddrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a three port embodiment of the MicroFlex Scope with asingle tool port passing through the ultra-flexible tip.

FIG. 2 illustrates a three port embodiment where all three ports passthrough the ultra-flexible tip.

FIG. 3 illustrates a MicroFlex Tool variation of the invention, where atool is permanently affixed to the actuated cathether, and this isinserted into a conventional catheter or endoscope.

FIG. 4 illustrates a MicroFlex Tool Guide variation, where the actuatedcatheter contains a single port for a disposable tool.

FIG. 5 illustrates a MicroFlex Scope Guide variation, where the actuatedcatheter contains a single large port to guide a conventional catheteror endoscope.

FIG. 6 illustrates a MicroFlex Tip containing an ultra-flexible actuatedtip that can be added to a conventional catheter or scope withoutsignificantly increasing the instrument diameter.

FIG. 7 illustrates a cross-section of an actuator element of theinvention

FIG. 8 provides a schematic diagram of one embodiment of a demultiplexercircuit located at each actuator, which enables sensing and controlsignals to be routed to each actuator element individually.

FIG. 9 illustrates a layout of an actuator lattice, containing threestrings of two actuator elements each.

FIG. 10 illustrates a close-up of the layout of each layer comprising anactuator element.

FIG. 11 shows a photograph of a large scale, stainless steel prototypeof the actuated coil skeleton

FIG. 12 outlines an example construction method for actuator elements.

FIG. 13 outlines an example construction method for demultiplexingcircuits on a silicon substrate.

FIG. 14 illustrates an welding fixture for assembling an actuatorlattice onto a coil skeleton spring to fabricate a MicroFlex instrument.

FIG. 15 illustrates a cross section of a three port MicroFlexinstrument.

FIG. 16 illustrates a cross section of a one-port MicroFlex instrument.

FIG. 17 shows a block diagram of a temperature and strain feedbackcontrol system for tracking of operator motion commands.

FIG. 18 shows an example of the performance of a control systemnumerical simulation with and without temperature feedback.

FIG. 19 shows the temperature excursions obtained during the trackingsimulation of FIG. 18.

FIG. 20 shows the temperature hysteresis present in the shape memoryalloy model used in the simulation of FIG. 18.

FIG. 21 shows an example embodiment of the electronics used to implementthe control system of FIG. 17.

FIG. 22 illustrates an exemplary direct visualization capability of animage guide in accordance with an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Currently, minimally-invasive endoscopic surgery has widespreadapplications and will continue to evolve into the standard of care astechnology improves. Many diagnostic and surgical procedures thatinvolve small spaces and accessibility problems, including head and neckprocedures, sinus procedures, lung and airway procedures, neurosurgery,urology, and pediatric and neonatology procedures are likely to benefitfrom research and advances in endoscopic technology.

For instance, advances in endoscopes and improved external CT guidedimaging provide some assistance to the rhinologic surgeon. Withoutintending to be limited by theory, small, flexible tools that cannavigate through the small, tightly curving sinus structures and supportdirect visualization and direct access would have the followingpotential benefits: increased patient safety, reduced risk andcomplications, reduced surgical time.

Again, without limitation, in lung and airway applications, smallflexible endoscopes that could reach the peripheral airways couldprovide: new capability to perform direct visualization and samplingprocedures in small airways, requiring minimal additional exam time;thin, highly controllable visual and manipulative access to sites,reducing invasiveness, patient discomfort, recovery time, and risk;capability to perform procedures such as laser therapy, brachytherapy,electrocautery, cryotherapy, photodynamic therapy, placement of airwaystents, and balloon dilatation.

I. Introduction

To address current limitations, the present invention provides, in part,a dexterous endoscope apparatus, referred to herein as a MicroFlex Scope(MFS). The MFS is an novel, small diameter, e.g., less than about 1 mmto about 4 mm, about 1 mm to about 3 mm, etc., dexterous endoscope thatallows for access, direct visualization, tissue sampling, treatment,etc. of body lumens and adjacent tissue.

In one embodiment (FIG. 1) the distal end of the MFS of the invention isan ultra-flexible tip that comprises a plurality of thin, curved shapememory alloy (SMA) actuator elements 102 attached to at least onestructural skeleton, e.g., a coil spring skeleton 103 or hingestructure. The SMA actuator elements in each structural skeleton segmentproduce force in response to their temperature relative to specificthresholds. The SMA actuator element is compressed by the structuralskeleton when its temperature is low, causing each segment to be in areference state, e.g., curved and short 102″ if a coil skeleton is used.Each actuator element can be indirectly heated by a heater element,which causes the actuator to straighten 102′ thereby exerting a force onthe structural skeleton, e.g., pushing the coil spring apart where theactuator is attached. By individually controlling the temperature in allactuator elements, each segment can be bent in any direction and/orextended. By stacking up segments, the tip of the device can move in anydirection with an unprecedented range of motion for its size. FIG. 1also shows how a fiber optic image guide 104 may be integrated with theactuator elements to enable precise sampling or manipulation of tissue112 in small spaces. This embodiment also includes a vacuum/flush port105, illumination fibers 106, an electrical cable for sensing andactuation signals 107, and an internal channel 108 for actuator cooling.An outer sheath 101 encapsulates the endoscope and thermally separatesthe actuator elements from body tissue. In this embodiment, the toolport 109 is contained in the ultra-flexible tip, enabling a tool 110 tobe precisely manipulated by controlling the actuator elements, usingvisual feedback from the image guide to the surgeon.

The MFS concept is highly modular, enabling a variety of product forms.FIG. 2 shows a highly integrated, multiport MFS scope containing threeports in a carrier catheter 207 and an actuated tip 201. One port 203contains an image guide, and two ports 204, 205 are general purposeports for removable tools or vacuum/flush of fluids. This form containsthree actuators 202 per segment and a helical coil skeleton spring 206.FIGS. 3-6 show other product forms which may be developed from MFStechnology.

Heating of SMA actuator elements may generally be accomplished by directJoule heating, enabling resistance feedback for position sensing.However, the relatively large cross sectional area of the actuatorelements of the invention often require relatively large currents. Thecorrespondingly large connecting wires may generally limit jointbending, thereby reducing dexterity. As such, in accordance with certainembodiments of the invention, indirect heating of the SMA actuatorelements is used, wherein a heater element is interfaced with the SMA.Smaller heating currents and connecting wires are therefore required toheat the actuator elements of the invention, thereby enabling a novelintegrated temperature and strain sensing concept, described in furtherdetail herein.

In certain embodiments, the heater element may comprise an integratedheater/sensor element adapted to heat the actuator element and to sensethe temperature and bend state of the actuator element. Inconfigurations comprising a plurality of actuator elements,multiplexing/demultiplexing of heating currents and sensor voltages maybe accomplished via a parallel bus and demulitplexing circuit. In thisregard, a demultiplexing circuit using standard metal oxidesemiconductor technology may be designed to achieve individual sensingand control over each actuator element.

Without being limited by any particular theory or mode of operation, theMFS designs of the present invention allow for: safe navigation anddirect visualization over an increased area of various body lumens;enhanced flexibility and controllability via actuators in theultra-flexible MFS tip; accurate diagnostics, effective tissue samplingand treatment using the ultra-flexible and actively-controlled MFS tip;and a cost-effective, manufacturable design through innovations inactuation, control, and assembly that uses similar, modular componentsto construct tools tailored to a variety of applications.

The MFS represents integrated innovations in actuation, sensing, controland assembly at small scales that can produce an advanced generation ofscopes that are more flexible and controllable. Due to these designcharacteristics, MFS is uniquely positioned to make a significantcontribution to improving the, e.g., treatment of chronic sinusitispatients, or in the diagnosis and treatment of lung cancer throughdirect visualization, localization and more accurate sampling ofsmaller, peripheral lesions. The MFS may also be used to enhance otherprocedures where a bronchoscope is used, including diagnosis andtreatment of infections, diffuse lung diseases, and airway obstructions.The MFS may also benefit other medical specialists who must visualizeand maneuver in small spaces, including pediatricians, neurosurgeons,and ENTs. The MFS technology also has potential applications in manyother regions of the body, providing enhanced diagnostic access, directvisualization, and enabling new therapeutic procedures.

The following headings are intended for organizational purposes only,and are not intended to limit the scope of the disclosure in any regard.

II. Actuator Elements of the Invention

As described above, the distal end of the MFS of the invention comprisesat least one actuated structural skeleton including a plurality ofSMA-based actuator elements. The SMA provides superior capability toproduce large extension forces over large deformations through a simplebending action. These characteristics support the construction of verysmall (less than about 1 to about 4 mm, about 1 to about 3 mm, about 1to about 2 mm, etc. diameter), actively controlled devices that canreach into and maneuver in small, previously inaccessible body lumensand cavities. Because heating/cooling rates, and, thus, motion speeds,increase dramatically as devices are reduced in size, SMA actuation isideal for small devices. By way of example, required temperaturevariations are approximately 25° C. for nickel-titanium (NiTi) SMAalloys useful in connection with the present invention. This range canbe adjusted to be compatible for body temperature use by specifyingalloy composition. Several vendors now specialize in production of NiTialloy stock in a variety of forms and activation temperatures, as knownin the art. However, the invention is not so limited, and any suitableSMA known in the art may be used.

One known drawback of SMA materials in small-scale applications involvesissues with position control. These difficulties arise from hysteresisbased on the response of the material to temperature and stressconditions. Repeatable and accurate control of actuator positionrequires that this non-linear hysteresis characteristic be accuratelymodeled and compensated for in the control system. As described infurther detail below, the present invention, in part, address thesedifficulties by utilizing an innovative method of controlling thishysteresis, using an explicit temperature control loop in conjunctionwith a proportional-integral (PI) position control law to produceaccurate tracking of motion commands.

More particularly, control of the plurality of actuator elements in amulti-segment device may be supported, at least in part, in accordancewith the present invention by two aspects. The first is a parallel buswhich connects to all actuator elements, with correspondingdemultiplexing circuits for each independent actuator to enableindividual communication with each actuator and sensor. The second is anintegrated heater/sensor element that heats the SMA actuator material bysmall electric currents, while producing voltages that are proportionalto present temperature and bend state. These voltages are read by acomputer controller that adjusts heating current to cause the desiredmotion in the actuator element based on, e.g., the temperature and PIposition control loops.

A. Certain Configurations of Actuator Elements

In one aspect, the actuator elements of the invention may comprise: aSMA layer; an integrated heater/sensor layer interfaced with said SMAlayer; and a demultiplexing circuit and parallel bus interfaced withsaid heater/sensor layer. A cross section of an actuator element 700 isshown in FIG. 7. The SMA layer 701 is bonded to the heater/sensor layer703 by a strain isolation layer 702. The heater sensor layer is afive-layer arrangement of three polyimide layers 706, 708, and 710,sandwiching two metal layers 707 and 709. A demultiplexing chip 704 maybe included. The substrate 705 supports the construction of the actuatorelement, and is removed in final stages of fabrication. In addition, theactuator elements, the actuated structural skeleton, and/or the MFS maybe covered by an insulation sheath, so tissue may be shielded fromexposure to electrical actuation signals or excessive temperatures whenused in vivo. The SMA layer may, for example, range in thickness fromabout 10 μm to about 60 μm, depending on the size of the device and themagnitude of forces desired.

In accordance with the present invention, the SMA layer is adapted toexhibit a variation in bend state corresponding to a variation intemperature of the SMA layer. By way of example, a useful range ofmotion and force may be obtained with about a 20° C., about a 22° C.,about a 24° C., about a 26° C., about a 28° C., or about a 30° C.variation in temperature. In a basic form, this is accomplished byheating the actuators from body temperature (37° C.) to a maximum of,e.g., 67° C. for short periods. If desired, the exterior surface of theSMA layer may be thermally insulated to protect tissue from exposure toexcessive temperatures when used in vivo. Alternatively, the exteriorsurface of the SMA layer may be at least partially interfaced with aclosed circuit irrigation system configured to provide a chilled biastemperature state to the SMA layer. For instance, such a cold biasirrigation system may be achieved through a slow infusion of roomtemperature or chilled sterile saline through the catheter, which may beextracted through the suction port. In other embodiments, such chilledbias may be obtained via use of cooled sterile air, or other suitableliquid or gas. As such, in some embodiments, the SMA layer may comprisesa NiTi alloy with a bend state activation temperature between about 17°C. and about 67° C., more particularly, between about 17° C. and about37° C., between about 17° C. and about 47° C., between about 27° C., andabout 47° C., or between about 27° C. and about 57° C.

In certain embodiments, the heat/senor layer is adapted to heat the SMAlayer upon application of current to the heater/sensor layer, and tosense the temperature and bend state of the SMA layer by producing avoltage in proportion to the SMA temperature and bend state. Theelectrical power necessary to heat the actuator elements may be very lowdue to their small size. For instance, the maximum power for eachactuator may be in the range of about 1-10 mW. The heater/sensor layermay, in some embodiments, comprise two metal layers separated by adielectric layer. By way of example (FIG. 7), the heater/sensor layer703 may comprise a polyimide layer 708 deposited between sputtered metallayers 707, 708, e.g. amorphous Aluminum. The metal heater/sensor layersmay generally be about 0.1 μm to about 0.2 μm in thickness. and theinner polyimide layer thickness may be between about 0.3 μm and about1.0 μm, depending on actuator size and corresponding required bendradii. A protective polyimide layer may be include on top 706 and onbottom 710 to comprise the heater/sensor layer.

In certain embodiments, the two layers of the integrated heater/sensormay be connected electrically in series (R1 and R2 in FIG. 8), so thatcurrent through the heater/sensor heats the SMA layer for actuation,while the voltage and current are sensed to transduce the SMA layertemperature and bend state via resistance changes. As the SMA layerbends during actuation, a differential strain occurs in theheater/sensor layers, which is sensed via a change in voltage divisionratio at the center tap (Sen). This bending strain provides a directmeasure of the position, i.e., bend state, of each actuator element,since the heater sensor layer is attached to the SMA with an adhesivewhich causes the SMA and the heater/sensor layer to have the same bendradius. As the SMA is heated by the heater layers, the change in totalresistance due to the material temperature coefficient of resistance iscalculated from total voltage (Vdd to Vss) and current (into Vss) in theseries connection to provide a measurement of SMA temperature.

Further, the heater/sensor layer may optionally interface with the SMAlayer via a strain-isolating adhesive layer, e.g., a silicone adhesivelayer 702 (FIG. 7). By way of example, the stain-isolating adhesivelayer may be about 5 μm to about 30 μm in thickness, depending on thesize of the actutator element. Any suitable strain-isolating adhesiveknown in the art for such purposes may be used, and the thickness maydepend on the particular adhesive selected. The strain-isolatingadhesive layer may serve to attenuate the large strain in the SMA layer(about 1 to 4 percent) to levels which prevent fatigue failure in theheater/sensor layer (about 0.1 percent). This strain-isolation layer mayalso prevent buckling of the heater/sensor layer as the SMA layer bendsduring actuation.

The silicon demultiplexing chip (FIGS. 7,8) and parallel bus may beadapted to allow for connection of multiple actuator elements therebyenabling communication and control of individual actuator elements whenmultiplexed with a plurality of actuator elements. The parallel bus maypreferably comprise a multi-wire flex cable bus system configured tointerconnect multiple actuator elements. The interconnection may be amulti-wire bus, e.g. six wires, wherein the multi-wire bus is configuredsuch that one wire supplies heater current, one provides a currentreturn, one provides a strain sensing voltage, one provides a logicground, and the other two wires provide handshake enable signals. Inthis embodiment, the enable signals produce a daisy-chain that connectseach heater/sensor to the bus through, e.g., FET switches, one at atime, multiplexing sensing and actuation through all actuator elementsin the actuated structural skeleton. The demultiplexing circuit issimple, enabling silicon chips to be small enough to be located on eachactuator element, enabling high dexterity in a small diameter actuatedcatheter.

By way of example, as shown in FIG. 8, a chain-type demultiplexingscheme may be used in which one stage locks out the following stagewhile it is active, enabling the subsequent stage as it deactivates.This passes active control and sensing connections to each actuator inturn, through the last actuator in the chain. This process is repeatedat high rates relative to the heating time constants (e.g., severalhundred cycles per second), producing desired average heating andcorresponding actuation motions. During each heating cycle, only oneactuator heater/sensor is connected to Vss, Vdd, and the center tapsense line Sen via FET switches, enabling each actuator to beindividually sensed and controlled.

Generally, up to about 30 actuator elements may be served via a singleparallel bus, based on the peak currents allowed by power switches andbus conductors currently available in the art. However, the number ofactuator elements may vary depending on the exact components used. Byway of example, in certain embodiments, the parallel bus will haveon-resistances in each segment less than 1/30 of the correspondingactuator heater resistances, and will carry peak currents of at least 30times the average heater current to enable time-division multiplexing ofup to about 30 separate heater elements. Other embodiments may haveseveral actuators ganged together, heating and sensing the severalactuators with a single demultiplexer stage. This reduces the number ofdemultiplexer chips required in the device, but also reduces the numberof degrees of freedom that can be independently actuated. In anotherembodiment, demultiplexer chips are not used. Instead, one, two, orthree strings of actuators are operated by separate parallel busses,producing one, two, or three degrees of freedom in motion, but withreduced device complexity and cost. Each string of actuators in thisembodiment may include one or more SMA actuator elements, withcorresponding heater/sensor layers, connected electrically in parallel.The bus for each string may be simplified, requiring only three wires(Vss, Vdd, and Sen) when demultiplexer chips are not utilized. Such athree wire bus is shown in FIG. 10.

B. Fabrication of Actuator Elements

Efficient manufacturability is of concern in developing new technology.Assembly of complex devices with sub-millimeter components has beentechnically challenging and cost-prohibitive, unless the entire devicecan be fabricated using photolithography processes, as inmicroelectronic circuits and, more recently, microelectromechanicalsystems (MEMS). However, these devices are limited to a planar2-dimensional structure. In accordance with the present invention, ithas been found that the actuator elements may be fabricated as planarcomponents manufactured using photolithography, and then assembled into3-dimensional structures using an innovative rolling weld techniquedescribed below. These techniques are simple and parallel in nature,supporting low cost, mass manufacturing.

In one aspect, a method of making all actuators in the device on acommon substrate is provided. The actuators are arranged into a flatmulti-element lattice containing one or more strings of actuatorelements, and one or more segments of actuators on a common bus in eachstring. FIG. 9 shows a lattice containing three strings of two segmentseach. In accordance with one embodiment of the invention, scaling andeconomic manufacture of the actuator elements described herein may beachieved based, in part, on lithography processes that can produce thesmall features of the actuator elements of the invention. In anexemplary embodiment illustrated in FIG. 10, the actuator elements maybe designed as laminated structures comprising: the SMA layer with avariable thickness produced by a front 1001 and back 1002 etch pattern;a strain-isolating silicone adhesion layer; and an integratedheater/sensor layer 1003, 1004. The interconnecting bus 1005 is alsoprovided on the same layer as the heater 1003. The optionaldemultiplexing chip 1006 is also shown. Generally, this embodimentrequires methods for: providing/fabricating lithography masks foractuator elements; providing/fabricating a patterned SMA layer;providing/fabricating heater/sensor/bus layers; bonding SMA andheater/sensor/bus layers together to form an interconnected actuatorlattice; and releasing from carrier substrates as needed. With referenceto FIG. 10, an exemplary method (FIG. 12) comprises providing apatterned SMA layer 1210 fixed to a peripheral handling frame. Anintegrated heater/sensor layer 1220 fixed to a carrier substrate isprovided, including a parallel bus fixed to the carrier substrate andelectrically connected to the heater/sensor layer, As will be understoodby those skilled in the art, the steps of blocks 1210, and 1220 maygenerally be performed in any order desired.

Moving on, an adhesive silicone layer 1240 is deposited onto theheater/sensor/demultiplexer layer and cured. The SMA layer is thenpositioned over the heater/sensor/demultiplexer/adhesive layer via amask aligner such that alignment marks on the two patterns correspond.Once aligned, the SMA layer is pressed onto the heater/sensor layer toeffect a permanent bond. The carrier substrate is removed from theassembly by a back-side etch, during which the front-side layers areprotected by a temporary etch resist (block 1250). Following substrateremoval, the completed actuator lattice is handled via the peripheralSMA handling frame.

Optionally, a demultiplexing circuit may be included (block 1230). SMAthin film patterns in SMA are provided as in block 1210, Theheater/sensor/demultiplexer layer, as in block 1220 is a sandwich ofpolymer (e.g., polyimide) between meander-pattern metal films (e.g.,amorphous Al), but now is electrically connected to silicondemultiplexing chips, which are first produced on a silicon substrate(1230). These two layers may then be bonded together with, e.g., a softsilicone adhesive layer (1240), using a mask aligner to position the SMAframe and silicon substrate face-to-face over each other, subsequentlyforcing them together to effect attachment. Theheater/sensor/demultiplexer carrier substrate may then be removed by apatterned, anisotropic silicon back-side etch, using an apparatus whichrestricts etchant contact to the back side only (block 1260). Thefinished SMA/heater/sensor elements will generally remain electricallyconnected to each other in strings, and mechanically connected by theperipheral handling frame.

Fabrication of demultiplexing circuits on a silicon substrate mayutilize a variety of foundry processes. The example of FIG. 8 uses avery simple p-type enhancement-mode metal oxide semiconductor processthat requires only 4 photolithography masks, as described in detail inFIG. 13. Demultiplexing chips could be produced using other processes,however. For example, the load transistors (L1, L2, L3 in FIG. 8) couldbe provided by depletion mode devices, or complementary (n-type)devices.

The demultiplexing circuit (FIG. 8) at each actuator is simple,requiring very little silicon area, e.g. 200×200 μm, enabling a smallchip to be located at each actuator using the integrated fabricationmethod discussed above. This preferred method avoids the difficulty ofhandling and mounting of such small chips. However, the actuatorelements are not so limited, and, alternatively, separate manufacturingand subsequent mechanical and electrical connection of the heater/sensorelements to the demultiplexer circuit chips could be utilized, ifdesired.

In one embodiment, three buses may be fabricated in a lattice structureso that all mechanical and electrical connections to the actuators in a10 segment, 30 actuator structural skeleton may be accomplished on asingle substrate. By way of example, a 10-segment, 3-string lattice withhandling frame may be approximately 20 mm by 10 mm, enablingapproximately 10 complete MicroFlex sensing/control lattices to beobtained from a single 3 inch diameter silicon wafer.

III. Actuated Structural Skeleton Segments of the Invention

As discussed above, the distal end of an MFS of the invention comprisesat least one actuated structural skeleton segment which includes aplurality of actuator elements. The structural skeleton may be anysuitable skeleton structure which is capable of supporting a pluralityof actuator elements, deforming to a variety of bend states upon heatingof the actuator elements, and returning to a base state when theactuator elements are cooled. By way of example, the structural skeletonmay be a hinged structure, or preferably an elastic helical coilstructure. By varying the cross section diameter of the skeleton wire,as well as the SMA actuator cross section thickness, a wide variation inmechanical properties of the MFS can be obtained. Larger cross sectionsproduce larger force capabilities, but reduced range of motion. Smallercross sections enable more motion, e.g. smaller catheter bend radii, butlower force capability. Further, the structural skeleton may becomprised of a superelastic material (e.g., NiTi) to further enhance theactuator range of motion, enabling smaller catheter bend radii andenhanced dexterity for a given force capability, because the skeletonwire may be strained well past conventional limits without permanentyielding.

A. Configuration of Certain Actuated Coil Segments

As such, in one aspect, an actuated coil segment is provided comprisinga coil skeleton and a plurality of actuator elements. More particularly,in one embodiment, the actuated coil segment may include: a plurality ofSMA actuator elements interconnected via a lattice structure adapted toprovide skeleton attachment points, a SMA coil skeleton secured to theplurality of SMA actuator elements via the attachment points, and abutsthe lattice structure at other load-bearing points. The actuatorelements may be secured to the coil skeleton in any manner known in theart, such as welds, adhesives, bonding, etc. By way of example, when theskeleton spring is superelastic NiTi, the SMA actuator elements may besecured to the SMA coil skeleton via spot welds at the attachment pointsof the lattice structure, and via the mating of load-bearing features onthe coil spring skeleton with corresponding patterns in the SMA latticestructure. When the skeleton is another material, e.g. stainless steel,the SMA actuator lattice may be secured by welding a stainless steelband onto the skeleton, trapping the SMA layer at the attachment points.This is necessary because SMA does not weld well to other materials.FIG. 11 shows a photograph of a prototype that uses the welding bandapproach. The SMA actuator elements may include a SMA layer interfacedwith an integrated heater/sensor layer, as described herein.

The SMA actuator elements may be attached to the SMA coil skeleton insuch a manner so as to facilitate bending of the coil skeleton uponactuation of a variation in bend state of an actuator element. Forinstance, the plurality of actuator elements may be secured to the coilskeleton on the exterior surface of the coil and/or the interior surfaceof the coil, depending on the particular orientation of the actuatorelement. In certain embodiments, the SMA actuator elements may beinterconnected in a lattice structure, which may be secured to the SMAcoil skeleton such that the coil skeleton primarily contacts the latticestructure at the interconnection points. By way of example, the latticestructure may comprise at least two parallel segments of at least threeinterconnected SMA actuators elements. In other embodiments, the latticestructure comprises at least one series segment of at least one parallelSMA actuator each interconnected via the SMA lattice structure andparallel bus.

B. Fabrication of Actuated Coil Segments

Assembly of flat photo-etched components into a strong,three-dimensional device is difficult at small scales. As such, a novelmethod that is both simple and suitable for parallel automation atreduced costs was developed in accordance with another aspect of theinvention. However, the actuated coil segments of the invention are notso limited. With reference to FIG. 14, a method for fabrication anactuated coil segment of the invention is illustrated. The SMA actuatorlattice 1402, along with an optional welding strip 1406, is positionedover the welding mandrel 1403, which is inserted into the preformedskeleton spring 1401, axially stretched to the assembly length, andclamped with compression rings 1403 at each end. The welding stylus 1405is positioned over the assembly at desired locations, and spot welds areproduced by a resistance welder, whose electrodes are connected to thewelding mandrel 1403, and the welding stylus 1405. Welds between theskeleton spring and the actuator lattice occur where they contact underpressure between the mandrel and stylus. By repositioning the styluslaterally, a series of welds are produced along the skeleton axis,attaching one actuator string to the skeleton.

Then, the copper mandrel is rotated to wrap the actuator lattice aroundthe skeleton spring, and to position the welding electrodes at therequired positions for attaching the next string of actuators to theskeleton. After each string is welded to the skeleton, one weldingelectrode is connected to the SMA handling frame, so that when themandrel is energized, current flows laterally through the handlingframe, fusing anchor links 1407 to release the actuator strings fromtheir handling frame.

When all actuator strings are welded to the skeleton and released fromthe handling fame, the axial spring tension is released, therebyallowing the axial tension in the SMA coil skeleton to compress theplurality of SMA actuator elements inward, resulting in compressed-statecoil actuators in each coil segment.

Since the actuator elements then reside on the exterior of the coilskeleton, the electrical continuity of bus connections may be verified,and the SMA/heater/sensor/demultiplexer assembly may be visuallyinspected for any damage induced by the rolling weld assembly process.In certain embodiments, the process may result in two strings ofactuated coil segments including a plurality of elements each. In otherembodiments, three strings of actuated coil segments may be included.FIG. 15 shows a cross section of the three-string assembly which hasthree actuator elements 1501 in each turn of the three-faceted skeletonspring 1502. This embodiment provides three interior ports 1503, andalso indicates an exterior welding band 1504, which would be necessaryfor a non-superelastic skeleton spring. FIG. 16 shows a two-stringvariant, with components corresponding to FIG. 15, which allows arelatively large single interior port compared to the device outsidediameter.

IV. MFS Control System

In another aspect of the invention, a novel control system is provided,which is able to address both temperature hysteresis and strainhysteresis behavior The control system is generally configured tomonitor and control actuation of individual actuator elements based atleast in part on feedback of sensed temperature and strain from theheater/sensor layers in each actuator to an applied heater current. FIG.17 shows a block diagram of the control system, where the physicalportion of the systems is indicated by the dotted box. The controlsystem contains two loops. The inner loop measures temperature T fromthe resistance of the series connection of heater elements bonded to thecorresponding actuator, based on a calibration of the heater elementtemperature coefficient of resistance (TCR). This measurement iscombined with the desired temperature Td in a proportional-integralcontrol loop to force the actuator temperature to track the desiredvalue. This loop compensates for the temperature hysteresis in the SMAactuator, which would otherwise cause the internal state of theactuator, described by the so-called martensitic fraction, to lag behindthe desired value with a detrimental effect on actuator positioningspeed and accuracy.

The outer loop in FIG. 17 measures actuator position by transducingbending strain in the heater/sensor layer to a voltage division ratio inthe series connection of heater elements which is proportional to SMAlayer strain. This measured position L is then compared to the desiredreference position Lr in another proportional-integral control loop toforce L to track Lr. FIG. 18 shows the results of a detailed simulationof this control system tracking a varying position reference Lr which isrepresentative of motions that may be required in a surgical procedure.Note that the tracking error is very small, and the static accuracy atthe end of the motion is very good for the combined strain andtemperature control system. Tracking is poor with the strain feedbackloop alone. FIG. 19 shows the corresponding SMA temperature excursionsduring tracking, indicating the combination of temperature and strainfeedback provides superior tracking performance without substantialincreases in temperature excursion. FIG. 20 shows the temperaturehysteresis present in the physical model in these simulations, which isrepresentative of measured behavior in SMA materials.

Any suitable electronics may be used to implement the temperature andstrain control loops of the invention. The electronics should be capableof interfacing with the demultiplexing circuits and parallel bus(s) ofthe actuator elements, as well as to a suitable user control interface.Either analog or digital control may be utilized By way of example, FIG.21 shows an overall system diagram of one embodiment of the invention.As shown in FIG. 21, the control system 2100 may comprise a computerbased Controller 2101, and A/D Digital I/O Card 2102, and a Custom BusDriver Board 2103. Controller 2101 may interface with Card 2102 via I/OBus 2104, and Card 2102 may interface with Driver 2103 via 2 A/D, 2 DigOut, and Ground bus 2105. Further, Card 2102 may also interface with aUser Control Interface 2107 via, e.g., 4 A/D and Ground bus 2106. Driver2103 interfaces with Demultiplexing Chips 2122 via multi-wire bus 2121,and Demultiplexing Chips 2122 are interfaced with the IntegratedHeater/Sensor Layer 2123 bonded to actuator elements of an MFS System2120.

V. MicroFlex Scope (MFS) Apparatus and Methods of Use

As discussed above, in another aspect of the invention, an MFS apparatusis provided which comprises at least one actuated structural skeleton.More generally, an MFS apparatus of the invention is a microdexterousendoscope apparatus which comprises a manipulatable catheter. Thecatheter includes a lumen comprising at least one port in the interiorof the lumen and at least one actuated structural skeleton at the distalend of the catheter. As described above, the actuated structuralskeleton generally comprises a plurality of indirectly heated shapememory alloy (SMA) actuators secured to a SMA structural skeleton,wherein each SMA actuator is adapted to exhibit a variation in bendstate corresponding to a variation in temperature of the SMA actuator.In certain embodiments, the actuated structural skeleton is an actuatedcoil segment comprising at least one port in the interior of theactuated coil segment.

The MFS may further comprise a control system configured to monitor andcontrol actuation of the actuated structural skeleton(s), e.g., bymonitoring and controlling at least one coil segment, based at least inpart on, e.g., temperature and strain feedback from the actuatedstructural skeleton(s). The MFS also includes an electrical bustraversing the length of the catheter, which electrically interfaceswith the at least one actuated structural skeleton and the controlsystem. In certain embodiments, the control system may be adapted tomodulate application of a current to thereby independently control thetemperature of the plurality of SMA actuators to achieve a desired bendstate based at least in part on a non-linear hysteresis control modelusing feedback voltages obtained from the SMA actuator via theelectrical bus.

The MFS may be controlled by a user via a stylus attached to the base ofthe endoscope instrument. Motion of the stylus provides commands to acontrol system, which provides current to heat actuator elements in theMFS tip, causing the tip to track stylus motions. The four wiresensor/actuator bus and associated demultiplexing chips at each actuatorallow for control of the position of many actuator segments in the MFStip without requiring a large number of connecting wires along thelength of the MFS catheter.

By way of example, FIG. 1 shows an enlarged view of one embodiment of anMFS of the invention as it might be used to visualize and biopsy a smalllesion in a body lumen. The distal end of the device 100 containsseveral actuator segments 102, that can bend under the command of theoperator, extending 102′ (upon heating) or contracting 102″ (uponcooling) the structural skeleton at each segment. This gives the distalend snake-like dexterity to angulate in any direction and access thebody lumen ahead and to the sides of the catheter tip with fine controlover tip position and applied tissue forces. In the exemplifiedembodiment, the MFS will have three ports. One port 104 may, e.g.,contain an optical fiber scope for direct visualization. A second port109 may serve as a tool port (e.g., 110 biopsy brush, knife, curette,rotary burr, laser cautery, etc.), and a third port 105 may supportvacuum/flush procedures, e.g., to remove tissue fragments or to cleanthe fiber scope lens. In this embodiment, the tool is dextrouslymanipulated by the actuated distal end. Smaller optical fibers 106 maybe included within the lumen of the MFS to provide illumination of thevisual field. Further, an optional inflatable cuff 110 and inflationtube 108 may be used to stabilize the tip, distend tissue for betteraccess, localize lavage fluids, etc. Electrical connection to sense andcontrol actuator elements is provided by a multi-wire cable 107. Aninsulated sheath 101 encapsulates the catheter.

FIG. 2 illustrates an alternative embodiment of an MFS of the invention,as it might be used to navigate a body lumen and to manipulate tissue indistant cavities, e.g. in the sinuses. The distal end 201 of the device200 contains three ports 203, 204, 205 surrounded by several actuatorelements 202 that can individually bend under the command of theoperator. Again, this gives the tip snake-like dexterity to provide finetool control for access to tissue in the center of the passage, as wellas on the sides. In certain embodiments, the actuators may be spacedalong the length of the catheter at predetermined locations such thatthe proximal portions of the catheter follow the same path as the distalend of the catheter. The control system may be configured so as tofacilitate such actuation of the proximal portions to follow the distalend of the catheter. In this embodiment, all three ports are angulatedwith the actuator segments, moving the tool (e.g., in port 204) togetherwith the field of view (e.g., an image guide in port 203), as well as anauxilliary port 205 which may be used for a second tool, vacuum/flush,etc.

In certain embodiments, the ultra-flexible distal end of the MFS may becontrolled by an operator using a manipulative such as a stylus. Motionof the stylus produces commands for the actuators of the MFS through acomputer control system. The control system senses actuator elementposition (e.g., bend state) and causes heating in the element to producebending motion. This causes the flexible tip, e.g., as seen through theimage guide 104 in the remote visual field, to follow the stylus motioncaused by the operator's hand. Alternatively, the field of view is movedby the stylus, e.g. as in the device 200. Various tools may be insertedthrough the tool ports (109 or 204, 205) during a procedure to enable awide variety of diagnostic and therapeutic options

Further, as shown in FIG. 2, the image guide (e.g., in port 204) may bethe limiting factor in the MFS catheter flexibility. As such, in certainembodiments, e.g., FIG. 1, the image guide 104 may terminate at theproximal side of the distal end of the catheter, leading to aconfiguration wherein only the tool port 109, and not the image guide,passes through the distal end of the ultra-flexible tip.

Another embodiment of the MicroFlex technology is shown in FIG. 3, wherethe actuated skeleton does not contain a leumen. Instead, a tool isfixed to the distal tip. The resulting MicroFlex Tool (MFT) may beinserted into a conventional catheter or scope tool port, providing ahighly dextrous appendage at the tip for tissue sampling ormanipulation. Another MicroFlex Tool, e.g., a knife, may be substitutedby withdrawing the first tool and inserting the second. This providesthe simple, low cost, disposable MicroFlex capability.

A MicroFlex Guide (MFG) embodiment is shown in FIG. 4, where the MFGcontains a single lumen for a removable tool. This enables the MFGcomponent to be reused, if desired, and supports a variety of disposabletools. The MFG may be inserted into the tool port of a conventionalscope, which provides the image guide needed for visualization duringmanipulation of the ultra flexible tool guide.

The MicroFlex Scope Guide (MFSG) embodiment is illustrated in FIG. 5.This enables conventional scope or catheter to bend more dexterously byproviding actively controlled joints along the length of the scope, oronly at the tip, depending on the intended application. Here the MFSGhas a single large lumen, through which the conventional scope orcatheter is inserted. Once inserted into the body, the MFS Scope Guidecan provide a fixed passageway for fast re-insertion of a variety ofdifferent catheters or tools.

FIG. 6 shows another embodiment, where a MicroFlex Tip provides a largelumen for insertion of a conventional scope or catheter in anon-actuated sheath, which enables a highly dexterous tip to be added toa standard scope with little change in outside diameter, extending thecapability of existing scopes into new areas or new procedures.

Since the working components of the MFS device will be sealed againstcontact with tissue, sterilization will generally be an issue primarilywith the tool and flush ports. These ports are small, but can beforce-flushed with sterilization solution prior to re-use. Further,inserted tools may generally be disposable or sterilized separatelyprior to use.

In particular embodiments, a MFS apparatus of the invention may be usedin sinus surgeries; lung and airway diagnosis, sampling and treatment;and other endoscopic diagnostic, treatment and surgical procedures knownin the art. For instance, the methods of the present invention areuseful in neurosurgery, urology, respiratory care, chemoprevention,pediatrics, neonatology, and other ENT applications.

In one embodiment, a MFS of the invention may be used in sinusapplications to support direct visualization and access for diagnostic,treatment, and surgical procedures. In such embodiments, the diameter ofthe MFS endoscope will, e.g., be about 3 mm. In other embodiments, a MFSof the invention may used in lung and airway applications to supportdirect visualization and access for diagnostic, treatment and surgicalprocedures. For instance, the MFS may used in canulating and samplingfor biopsy in an accurate manner so as prevent perforation of thebronchi. In such embodiments, the diameter of the MFS endoscope will,e.g., be about 1 mm.

In one embodiment, the MFS of the invention may be used in a diagnosticmethod for the identification of endobronchial lesions. As describedherein, the MFS of the invention enables access into the peripheralairways thereby enabling direct visualization and sampling of lesions.Further, the MFS of the invention provides a novel platform, e.g., viathe tool port, for application of laser therapy, brachytherapy,localized chemotherapy, electrocautery, cryotherapy, photodynamictherapy, placement of airway stents, and balloon dilatation to relieveairway obstruction caused by malignant and benign airway lesions.

In sum, while a number of surgical instruments have facilitatedendoscopic procedures, without intending to be limited by theory, theMFS technology offers several distinct advantages that improve thequality of care, including: (i) support of direct visualization, access,and real-time imaging; (ii) access to previously inaccessible regions ofthe body; (iii) improved maneuverability and precise positioning; (iv)active controlled tip which supports a variety of tools; and/or (v)minimization of complications and postsurgical morbidity by supportingprecise surgery and minimal trauma to the body cavities, e.g., nasalstructures and airway passages.

EXAMPLES Example 1 Direct Visualization

An investigation of the optical quality provided by the image guide inthe catheter has been conducted. In one run, a 1.0 mm nominal outsidediameter of a fiber bundle, consisting of fibers approximately 4 μm indiameter, supporting approximately 30,000 fibers was used for imagetransmission. Lenses on the fiber tip can provide a depth of field from1 mm up to 10 mm, with an angular field of view of 55 degrees. Thebending radius of these image guides is as small as 30 mm.

Another experiment was constructed with approximately 3000 image guidefibers, surrounded by an illumination fiber ring. FIG. 22 shows an imagerecorded with this scope, taken at a distance of approximately 5 mm froma printed target. The ink letters are approximately 2 mm high, and areclearly identifiable. When magnified in a still image like this,individual fiber pixels are visible, and the image becomes noticeablygrainy. However, this pixilation is reduced considerably in live videoimages, due to image motion across the fibers, resulting in a sharperapparent image. In both cases, review by a pulmonary medical advisorindicated that this resolution should meet, e.g., bronchial mucosa examrequirements.

Lenses on the fiber tip can provide a depth of field from 1 mm to 10 mm,with an angular field of view of 55 degrees. This field of view can becanted to support visualization of the sides of the passage by combininga small prism with the distal lens. The bending radius of these imageguides is as small as 10 mm, which is smaller than the bend radius ofthe conventional bronchoscope through which the MFS passes, and issuitable for navigating the branches of the many body cavities includingthe peripheral airways. As described above, the image guide may be thelimiting factor in the MFS catheter flexibility, leading to anembodiment wherein only the tool, and not the image guide, passesthrough the most distal end of the ultra-flexible tip (see FIG. 1).

Example 2 Clearing Secretions and Blood

Clinicians routinely employ proven methods such as saline flush andadministration of selected drugs to thin mucous, decrease secretions andminimize bleeding during procedures. Recent clinical studies employingfluorescence imaging techniques have refined these secretion reductiontechniques. A flush/suction port has been incorporated into certainembodiments of the MFS design and located close to the distal lens ofthe image guide to clear material on or in front of the lens.

SAMPLE SUCTION RATE (seconds/ml) Saline 22 Saline/Airway Secretion (1:1Mix) 29 Saline/Whole Blood (1:1 Mix) 42

As shown in the table above, testing conducted with a sample smalldiameter catheter suitable to fit within the MFS demonstrated thefeasibility of removing blood and airway secretions through this port.Secretion samples at room temperature were removed from the catheterusing Standard Wall Suction, used for bronchoscopy, with salineaspiration between each test to clear the tubing. Assuming the use ofappropriate procedures to flush and thin secretions, the removal ratefor all substances should be more than adequate to handle the typical0.1-0.3 ml bleeding encountered in a distal airway. This testingdemonstrates that the MFS flush/suction port should be able to clearsmall amounts of airway secretions and blood away from the tip of theinstrument in distal airways.

Example 3 Prototype Model Actuated Coil Segment

A method similar to that described with reference to FIG. 15 was used togenerate a prototype device in stainless steel. Such prototype assemblyuses a technique that first rolls and spot welds the actuator elementstrings over a coil spring skeleton, using a copper stylus and coppermandrel as resistance welding electrodes, selectively energized toproduce welds at the points where they cross. FIG. 11 shows a model instainless steel constructed by similar process. When the welds arecomplete, the coil ends are released from their fixtures, allowing theaxial tension in the coil to compress the actuator elements inward,resulting in a final structure as illustrated in FIG. 1.

The invention has now been described in detail. However, it will beappreciated that the invention may be carried out in ways other thanthose illustrated in the aforesaid discussion, and that certain changesand modifications may be practiced within the scope of the appendedclaims. Accordingly, the scope of this invention is not intended to belimited by those specific examples, but rather is to be accorded thescope represented in the following claims.

What is claimed is:
 1. A microdexterous endoscope apparatus comprising:a catheter with fixed tool tip, or having a lumen comprising at leastone port in the interior of said lumen; at least one actuated segment atthe distal end of the catheter, wherein the actuated segment comprises aplurality of indirectly heated shape memory alloy (SMA) actuatorssecured to a flexible skeleton, wherein each SMA actuator has a biasingspring operatively associated therewith, the biasing spring biasing theSMA actuator to a select bend at a reference state, the SMA actuatorhaving a thermal conduction barrier between any adjacent SMA actuator,the SMA actuator being adapted to exhibit a variation in bend statecorresponding to a variation in temperature of the SMA actuator; acontrol system configured to monitor and control actuation of said atleast one actuated segment based at least in part on temperature andstrain feedback from said plurality of SMA actuators; and a parallelelectrical bus traversing the length of the catheter and interfacingwith the plurality of SMA actuators of said at least one actuatedsegment and said control system; wherein the control system is adaptedto modulate application of a current to thereby independently controlthe temperature of each of the plurality of SMA actuators to achieve adesired bend state of each SMA actuator based at least in part on thecontrol system being capable of compensating for the non-linearhysteresis in the SMA actuator using feedback voltages obtained from theSMA actuator via the electrical bus.
 2. A microdexterous endoscopeapparatus of claim 1, wherein said catheter comprises a plurality ofactuated segments located along the length of said catheter, and saidcontrol system is adapted so as to control actuation of said actuatedsegments such that the proximal end of the catheter follows the samepath as the distal end of the catheter when used in vivo.
 3. Themicrodexterous endoscope of claim 1 wherein the flexible skeletoncomprises the biasing spring.
 4. The microdexterous endoscope of claim 3wherein the flexible skeleton comprises a coil spring.
 5. Amicrodexterous endoscope comprising: a catheter with fixed tool tip, orhaving a lumen comprising at least one port in the interior of saidlumen; and at least one actuated segment at the distal end of thecatheter, wherein the actuated segment comprises a plurality of radiallyspaced shape memory alloy (SMA) actuators secured to a flexibleskeleton, wherein each SMA actuator comprises a SMA layer having a firstend and a second end with a biasing spring operatively associatedtherewith, the biasing spring biasing the SMA actuator to a select bendat a reference state between the first end and the second end, each SMAlayer having a thermal conduction barrier between an adjacent SMA layerand wherein each SMA layer is adapted to exhibit a variation in bendstate corresponding to a variation in temperature of the SMA layer, eachSMA layer being operatively associated with the flexible skeleton toflex the skeleton upon a variation in bend state.
 6. The microdexterousendoscope of claim 5, wherein each SMA actuator further comprises: aheater operatively associated with each SMA layer to indirectly heat theSMA layer to vary the bend state of the SMA layer.
 7. The microdexterousendoscope of claim 6 wherein each heater comprises an integratedheater/sensor layer interfaced with the SMA layer, the heater/sensorlayer being configured to indirectly heat the SMA layer upon applicationof current to the heater/sensor layer, to sense the temperature and bendstate of the SMA layer, and to produce a voltage in proportion to thesensed temperature and bend state of the SMA layer.
 8. Themicrodexterous endoscope of claim 7 further comprising a demultiplexingcircuit and parallel bus interfaced with each heater/sensor layer,wherein the demultiplexing circuit and parallel bus are adapted to allowfor connection of multiple actuator elements and thereby enablecommunication and control of individual actuator elements whenmultiplexed with a plurality of actuator elements.
 9. The microdexterousendoscope of claim 8 further comprising a control system connected tothe parallel bus, the control system being configured to monitor andcontrol actuation of the at least one segment based at least in part ontemperature and bend state feedback from the heater/sensor layers. 10.The microdexterous endoscope of claim 9 wherein the control system isadapted to modulate application of a current to thereby independentlycontrol the temperature of the plurality of SMA actuators to achieve adesired bend state of the SMA layer based at least in part on thecontrol system compensating for any non-linear hysteresis in the SMAlayer using feedback voltages obtained from the actuator via theparallel bus.
 11. The microdexterous endoscope of claim 7, wherein eachheater/sensor layer interfaces with the SMA layer via a strain isolatingadhesive layer.
 12. The microdexterous endoscope of claim 7, whereineach heater/sensor layer comprises two metal layers separated by adielectric layer configured to be capable of heating and sensingtemperature and bending strain.
 13. The microdexterious endoscope ofclaim 12 wherein at least one of the two metal layers comprises anamorphous aluminum.
 14. The microdexterous endoscope of claim 7 furthercomprising an exterior insulation sheath adapted to minimize exposure oftissue to electrical current or elevated temperatures when used in vivo.15. The microdexterous endoscope of claim 5 wherein the SMA layercomprises a Ni Ti alloy with a bend state activation temperature betweenabout 17 deg. C. and 67 deg. C.
 16. The microdexterous endoscope ofclaim 5 wherein the flexible skeleton comprises the biasing spring. 17.The microdexterous endoscope of claim 16 wherein the flexible skeletoncomprises a coil spring.
 18. The microdexterous endoscope of claim 5further comprising a radial space between radially adjacent SMAactuators.
 19. A microdexterious endoscope comprising: a catheter withfixed tool tip, or having a lumen comprising at least one port in theinterior of said lumen; at least one actuated segment at the distal endof the catheter, wherein the actuated segment comprises a plurality ofshape memory alloy (SMA) actuators secured to a flexible skeleton,wherein each SMA actuator comprises: a shape memory alloy (SMA) layerhaving a first and second end, the SMA layer being biased from a planarconfiguration to a select bend between the first and second end at areference state by a spring force, the SMA layer being adapted toexhibit a variation in bend state corresponding to a variation intemperature of the SMA layer, there being a thermal conduction barrierbetween adjacent SMA actuator layers; an integrated heater/sensor layerinterfaced with said SMA layer, wherein said heater/sensor layer isadapted to indirectly heat the SMA layer upon application of current tothe heater/sensor layer, to sense the temperature and bend state of theSMA layer, and to produce a voltage in proportion to the sensedtemperature and bend state of the SMA layer; and a demultiplexingcircuit and parallel bus interfaced with said heater/sensor layer,wherein said demultiplexing circuit and parallel bus are adapted toallow for connection of multiple actuator elements thereby enablingcommunication and control of individual actuator elements whenmultiplexed with a plurality of actuator elements.
 20. Themicrodexterous endoscope of claim 19, wherein each heater/sensor layerinterfaces with the SMA layer via a strain isolating adhesive layer. 21.The microdexterous endoscope of claim 19, wherein each heater/sensorlayer comprises two metal layers separated by a dielectric layerconfigured to be capable of heating and sensing temperature and bendingstrain.
 22. The microdexterious endoscope of claim 21 wherein at leastone of the two metal layers comprises an amorphous aluminum.
 23. Themicrodexterous endoscope of claim 19 further comprising a control systemconnected to the parallel bus, the control system being configured tomonitor and control actuation of the at least one segment based at leastin part on temperature and bend state feedback from the heater/sensorlayers.
 24. The microdexterous endoscope of claim 23 wherein the controlsystem is adapted to modulate application of a current to therebyindependently control the temperature of the plurality of SMA actuatorsto achieve a desired bend state of the SMA layer based at least in parton the control system compensating for a non-linear hysteresis in theSMA layer using feedback voltages obtained from the actuator via theelectrical bus.
 25. The microdexterous endoscope of claim 19 wherein theflexible skeleton comprises a coil spring and the coil spring providesthe spring force biasing the SMA layer to the select bend at a referencestate.